Is Proteinuria Normal in Multiple Myeloma?
Understanding Proteinuria in the Context of Multiple Myeloma
Proteinuria is never considered normal, regardless of the individual or underlying condition. Its presence always indicates a disruption in kidney function or an underlying systemic disease. In patients with multiple myeloma, proteinuria may not present in the typical way seen in other kidney disorders, which often leads to misinterpretation or delayed diagnosis.
Why Proteinuria Occurs in Multiple Myeloma Patients
In multiple myeloma, malignant plasma cells produce excessive amounts of monoclonal light chains—also known as Bence Jones proteins. These abnormal proteins circulate in the bloodstream and are filtered by the kidneys. When present in high concentrations, they can overwhelm the renal tubules, leading to a condition known as myeloma kidney or cast nephropathy. This is one of the most common causes of kidney injury in myeloma patients.
The Hidden Nature of Proteinuria in Myeloma
A key challenge in diagnosing proteinuria in multiple myeloma is that standard urine dipstick tests often return negative for protein, despite significant kidney involvement. This happens because dipsticks primarily detect albumin, whereas the excess light chains in myeloma are not effectively picked up by this method. As a result, patients may notice persistent foamy urine—a classic sign of protein loss—but routine urinalysis fails to confirm it.
To accurately assess protein excretion in these cases, clinicians must order a urine protein electrophoresis (UPEP) or a quantitative urine free light chain assay. These specialized tests can identify and measure the exact levels of kappa and lambda light chains in the urine, revealing the true extent of renal damage.
Complications: Light Chain Deposition Disease and Amyloidosis
Beyond obstructing renal tubules, excess light chains can deposit in various parts of the kidney, particularly the glomeruli, leading to light chain deposition disease (LCDD). In some cases, these proteins misfold and form insoluble fibrils, resulting in AL amyloidosis—a serious complication where amyloid deposits impair organ function, especially in the kidneys, heart, and nerves.
When a myeloma patient presents with overt proteinuria—especially nephrotic-range proteinuria—it raises suspicion for concurrent amyloidosis or LCDD. Therefore, further evaluation through serum free light chain assays, tissue biopsies, and imaging may be necessary to confirm the diagnosis.
Diagnostic and Therapeutic Overlap
The good news is that treatment strategies for multiple myeloma also target the complications of light chain toxicity. Modern regimens—including proteasome inhibitors (like bortezomib), immunomodulatory drugs (such as lenalidomide), and anti-CD38 monoclonal antibodies (like daratumumab)—effectively reduce the production of abnormal light chains. By controlling the underlying plasma cell disorder, these therapies simultaneously mitigate kidney damage from light chain deposition and amyloid formation.
In fact, early initiation of targeted therapy has been shown to improve renal outcomes and even reverse dialysis dependence in some patients. Supportive care, including adequate hydration and avoidance of nephrotoxic agents, also plays a crucial role in preserving kidney function.
Conclusion: A Call for Vigilance and Specialized Testing
While proteinuria is not a typical feature detected by standard urine tests in multiple myeloma, its underlying mechanisms—especially related to light chain overload—are both common and clinically significant. Physicians should maintain a high index of suspicion in myeloma patients with unexplained kidney dysfunction or foamy urine. Specialized urine testing is essential for early detection and intervention, ultimately improving long-term prognosis.
With comprehensive diagnostic approaches and effective myeloma-directed therapies, many of the renal complications associated with this disease are manageable—if identified promptly.